Variant rs12722477 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384290.1(HLA-G):c.400C>A(p.Leu134Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,026 control chromosomes in the GnomAD database, including 12,937 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1957 hom., cov: 32)

Exomes 𝑓: 0.10 ( 10980 hom. )

Consequence

HLA-G
NM_001384290.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.102

Variant links:

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

HLA-G links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060731173).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.400C>A	p.Leu134Ile	missense_variant	3/7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11 link	c.400C>A	p.Leu134Ile	missense_variant	3/7	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22115

AN:

152090

Hom.:

1951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.0870

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0866

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.138

AC:

34138

AN:

247312

Hom.:

3010

AF XY:

0.136

AC XY:

18334

AN XY:

134724

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.296

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.0867

Gnomad NFE exome

AF:

0.0861

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.103

AC:

150062

AN:

1460818

Hom.:

10980

Cov.:

AF XY:

0.105

AC XY:

75993

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.0884

Gnomad4 NFE exome

AF:

0.0790

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.145

AC:

22135

AN:

152208

Hom.:

1957

Cov.:

AF XY:

0.147

AC XY:

10970

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.174

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.300

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.0870

Gnomad4 NFE

AF:

0.0866

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.0557

Hom.:

607

Bravo

AF:

0.155

TwinsUK

AF:

0.0704

AC:

261

ALSPAC

AF:

0.0804

AC:

310

ESP6500AA

AF:

0.219

AC:

660

ESP6500EA

AF:

0.0873

AC:

473

ExAC

AF:

0.136

AC:

16442

Asia WGS

AF:

0.324

AC:

1124

AN:

3478

EpiCase

AF:

0.0950

EpiControl

AF:

0.0991

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

.;T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.46

T;T;.

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.6

.;H;H

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.090

Sift

Uncertain

0.027

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.28

B;D;D

Vest4

0.032

MPC

1.4

ClinPred

0.076

GERP RS

0.56

Varity_R

0.29

gMVP

0.053

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over